Cell suspensions prepared from a transplantable rat pheochromocytoma will be used to study the mechanism by which ionophores stimulate catecholamine secretion. A number of carboxylic ionophores, including lasalocid and monensin, stimulate the secretion of catecholamine from phenochromocytoma cells, in vitro. The stimulation of catecholamine secretion by lasalocid and monensin is not dependent upon the presence of extracellular calcium. The ionophores on the release of calcium from intracellular membranes. Other studies will determine the effects of these compounds on the efflux of calcium from cells which have been pre-incubated with 45Ca. Lasalocid also causes an activation of tyrosine 3-monooxygenase, and an increase in the rate of catecholamine synthesis, in pheochromocytoma cells. The effect of lasalocid on catecholamine synthesis will be correlated with its effect on catecholamine secretion, and the effects of monensin on catecholamine synthesis will be investigated. Finally, the effects of ionophores on catecholamine synthesis and secretion in normal chromaffin cells will also be investigated.